The proposed research is designed to study the cellular and molecular basis of H-2 linked genetic control of immune responsiveness and immune suppression, and the role of I region genes in immunocompetent cell interaction. The primary goal is to test the hypothesis that I region gene products are a new class of antigen-specific T cell receptors, which derive their specificity for antigen from amino acid sequence microheterogeneity among a large number of different gene products. These products may also share amino acid sequences currently identified as Ia antigenic specificities. Antisera specific for restricted subregion of the I region will be produced in multiple donor-recipient combinations. These antisera will be used for determination of the lymphoid cell types bearing Ia molecules, and for detection and mapping of functionally separate classes of Ia molecules. Restricted anti-Ia sera will be used for isolating I region gene products for amino acid sequence studies. Anti-Ia sera will be used to characterize Ia positive T cell helper and suppressor factors which are antigen specific, as well as nonspecific helper factors produced by allogeneic lymphocyte interaction. Long-term bone marrow chimeras will be used to determine why T and B cells from these chimeras can collaborate effectively, while allogeneic T-B cell collaboration does not occur in acute mixing experiments.